Robot-assisted thoracoscopic surgery for lung cancer has been rapidly spreading in Japan since lobectomy and segmentectomy became covered by national insurance in 2018 and 2020, respectively. In the 2022 Lung Cancer Clinical Practice Guidelines, robotic surgery is recommended as Grade 2B and recognized as an option for minimally invasive surgery. Robotic surgery has good maneuverability, especially at the hilum, and can facilitate meticulous operations for blood vessels and bronchi and lymph node dissection of the hilum and mediastinum with high accuracy. Consequently, the more difficult the surgery, such as in cases of advanced cancer, surgery after preoperative therapy, and segmentectomy, the more attractive this approach is. Although there is no clear evidence supporting the advantages of robotic surgery for lung cancer surgery in Japan at present, with the advent of new devices and new surgical robots, further development is expected.

In 1995, Hellman and colleagues introduced the concept of oligometastasis, viewed as an intermediate stage between early and advanced cancer. By 2020, the classification proposed by the European Society for Radiotherapy and Oncology, among others, has come to be widely accepted. Recent years have seen a growing body of evidence on the treatment of oligometastasis in non-small cell lung cancer (NSCLC), which is now included in lung cancer treatment guidelines. This article addresses local ablative therapy (LAT) for oligoprogression in NSCLC, which aim to delay disease progression and maximize the effects of chemotherapy. Surgical resection and radiation therapy are the primary intervention methods adopted. Recently, evidence for stereotactic body radiotherapy has been accumulating, and its effectiveness in driver-mutation-positive NSCLC is now evident. US guidelines recommend continuing targeted therapies after LAT. Although there is increasing evidence to support the effectiveness of combining immune checkpoint inhibitors with radiation therapy, the abscopal effect has been shown to be mild. A deeper understanding of the clinical efficacy and safety of oligoprogression and LAT, and the optimization of intervention methods, may offer potential for long-term disease control in more patients.

Objective. Chemotherapy for lung cancer with interstitial lung disease (ILD) has not been unified and is often given empirically. Fewer reports exist concerning second- or later-line therapy than first-line therapy. We herein report a case series of patients treated with docetaxel (DTX) and ramucirumab (RAM) as second- or later-line therapy at our hospital. Previous studies have reported that vascular endothelial growth factor (VEGF) may be related to acute exacerbation of ILD; we therefore examined whether or not chemotherapy could be administered more safely with DTX+RAM (an angiogenesis inhibitor) than with DTX only. Methods. We retrospectively analyzed patients treated with DTX+RAM as second- or later-line therapy for non-small-cell lung cancer with ILD between April 2017 and April 2021. Results. We included seven patients with a median age of 66 years old. Six of the patients were male. In terms of histologic types, there were five cases of adenocarcinoma, one case of squamous cell carcinoma, and one case of not otherwise specified. In terms of ILD, four cases were idiopathic, including one case of idiopathic pulmonary fibrosis, which developed as exacerbation of ILD related to chemotherapy. The median overall survival was 274 days, and the median progression-free survival was 186 days. Conclusion. DTX+RAM is a regimen that will continue to be studied and analyzed as second- or later-line therapy for non-small-cell lung cancer with ILD.

Background. There are few reports on the efficacy and safety of immune checkpoint inhibiter (ICI) in patients with autoimmune diseases. Irradiation for systemic sclerosis patients has been reported to cause late adverse events and is not a favorable indication. We herein report a case of pulmonary adenocarcinoma complicated with systemic sclerosis in which chemotherapy combined with an ICI was successful, allowing radiotherapy to be avoided. Case. A 67-year-old man had been diagnosed with systemic sclerosis at 55 years old and been under treatment at another hospital. He was referred to our hospital, when he has had a complaint of a back pain and was noted abnormalities on his CT scan. After a close examination, he was diagnosed with pulmonary adenocarcinoma that metastasized to the thoracic vertebrae. The metastasis in the vertebrae extended into the spinal canal, but the patient had systemic sclerosis, so irradiation carried a high risk. Because the tumor expressed high PD-L1, chemotherapy with an ICI was finally selected. Both the primary tumor and metastasis in the thoracic vertebrae were remarkably reduced without serious adverse events. Conclusion. ICI administration to systemic sclerosis patients may be a treatment option. However, cautious consideration is required, as this approach may increase the frequency of exacerbation of preexisting disease and immune-related adverse events.

Background. Liver metastases are common in patients with small-cell lung cancer (SCLC) and are associated with a poor prognosis. Recent reports, mainly from abroad, have demonstrated the efficacy of palliative radiotherapy for liver metastases, but this therapy has not been widely used or reported in Japan. Case. Since late June, 20XX-1, a 76-year-old man had been treated with carboplatin, etoposide, and durvalumab for extensive-disease SCLC. After completing six treatment cycles, the patient was undergoing maintenance therapy with durvalumab. Owing to worsening of the primary lesion, liver metastases, and para-aortic lymph node metastases, the patient was admitted to our hospital on late February, 20XX, for treatment modification. Since more than 90 days had passed since the last dose of etoposide, a sensitive relapse was considered, and carboplatin plus etoposide therapy was initiated. However, back pain and jaundice appeared and became severe, requiring the initiation of regular opioid therapy. The symptoms were suggestive of capsular extension due to the rapid growth of multiple liver metastases, prompting whole liver radiotherapy (21 Gy/7 fr) to alleviate pain. There was a temporary increase in pain due to a flare reaction, requiring a temporary increase in opioid and steroid doses, but the symptoms rapidly resolved, and the patient was discharged with independent gait. The patient was subsequently readmitted and switched to amrubicin therapy. Approximately one month after whole liver radiotherapy, all symptoms and multiple liver metastases were under control. Conclusion. SCLC is radiosensitive and responds well to low-dose radiotherapy. Radiation-induced liver disease is unlikely to occur at low doses, and whole liver radiotherapy is considered effective even in patients with treatment-resistant SCLC.

Background. Radiation-induced brain necrosis occurs with edema after radiotherapy. It is often difficult to distinguish from a brain tumor. Case. A 50-year-old man with advanced lung adenocarcinoma who had received stereotactic radiotherapy for brain metastasis presented with consciousness disturbance and worsening cerebral edema. Brain magnetic resonance imaging (MRI) showed an irregularly shaped mass beside the resection site and a large area of brain edema. Because the brain edema had spread to the irradiated area, it was difficult to distinguish between the brain metastasis and radiation-induced brain necrosis. Steroid therapy was started to treat the brain edema, and the cerebral edema decreased. No uptake of ¹¹C-methionine was seen in the mass on ¹¹C-methionine positron emission tomography (PET), so radiation-induced brain necrosis was diagnosed. Conclusion. When it is difficult to distinguish radiation-induced brain necrosis from brain tumors, we need to carefully conduct imaging examinations, such as brain MRI and ¹¹C-methionine PET.

Background. Cytokine releasing syndrome (CRS) is one of the most serious immune-related adverse events (irAEs) associated with the combination of immune checkpoint inhibitors (ICIs) and chemotherapy. Early therapeutic intervention is important to prevent a severe outcome. Case. A 72-year-old man underwent surgery for adenocarcinoma of the right lower lobe of the lung. During postoperative follow-up, he developed recurrent pleural dissemination. We treated him with nivolumab plus ipilimumab with chemotherapy. He had no major adverse events. On day 27, he was admitted to the hospital due to dyspnea caused by pleural effusion. After thoracic drainage, we performed pleurodesis on him on day 35. He had a persistent high fever from day 38; on day 45, he developed an impaired consciousness and multiple organ failure. Because CRS was suspected, we treated him with steroid pulse therapy and tocilizumab, and his symptoms improved. His condition stabilized temporarily, but he eventually died of pneumocystis pneumonia. Conclusion. During combination therapy with ICIs and chemotherapy, clinicians should consider the development of serious irAEs, such as CRS, and treat them promptly and manage them appropriately.

Background. We encountered a case of epidermal growth factor receptor (EGFR) gene mutation-positive lung adenocarcinoma that recurred 16 years postoperatively with subcarinal lymph-node metastasis alone. Case. A 65-year-old woman developed dyspnea. On an examination at a local hospital, right pleural effusion was found on chest radiography, and computed tomography of the chest revealed a 3-cm lung tumor in the right upper lobe of the lung with dissemination. She was diagnosed with right lung cancer (cT3N1M1a stage IVa) and treated with gefitinib starting September 2005. Three months later, salvage surgery was performed because of dissolution of the pleural effusion and shrinkage of the primary lesion. Gefitinib was continued postoperatively, and there was no recurrence for several years. Sixteen years after the surgery, an elevation of tumor marker levels was observed, and a close examination revealed left breast cancer and an enlarged subcarinal lymph node. The left breast cancer was treated with left mastectomy, and simultaneously, the subcarinal lymph node was excised. The lymph node was histopathologically diagnosed as metastasis of the lung cancer that had been excised 16 years earlier. Postoperatively, afatinib was administered, and the patient has survived without recurrence for 1 year and 11 months since the surgery. Conclusion. There have been few reports of long-term gefitinib administration and lung cancer recurring 16 years postoperatively. Further research is necessary to identify factors indicative of resistance to treatment after long-term gefitinib administration.

Background. Lorlatinib has shown excellent antitumor activity and central nervous system metastases control. We herein report a lung adenocarcinoma patient harboring ALK fusion who developed severe psychotic symptoms due to lorlatinib. Case. A 32-year-old never-smoking man was diagnosed with advanced lung adenocarcinoma harboring ALK fusion. He had no history of psychosis. He had been treated with alectinib for five years and six months. When lorlatinib was introduced as second-line treatment after tumor progression was observed due to cancerous meningitis, he developed a mild confusional state on day 8 of treatment, and on day 9, he threw himself from his third-floor apartment in an acute confusional state with visual and auditory hallucinations. Luckily, no high-energy trauma was observed. The patient showed improvement after withdrawal of lorlatinib and inward treatment at a psychiatric hospital, including anti-psychotic drug administration. Since the patient had no history of psychosis and had shown no similar symptoms during five years of hospitalization, we diagnosed him with a Grade 4 psychiatric disorder induced by lorlatinib. Conclusion. Although extremely rare, lorlatinib can cause serious psychiatric symptoms. Adequate explanation of this possibility is required at the time of induction, and if severe psychiatric symptoms are observed, collaboration with a psychiatrist is necessary.

Background. We experienced two patients with advanced non-small cell lung cancer (NSCLC) who were successfully treated with antineoplastic therapy after resection of a symptomatic solitary brain metastasis. Case 1. A 50-year-old man with advanced strongly PD-L1-positive NSCLC was treated with pembrolizumab after surgical resection of a brain metastasis. Severe enteritis developed after four courses of pembrolizumab treatment and was controlled with steroid therapy. Despite the interruption of further treatment due to adverse events, no tumor progression was observed at 27 months after the final administration of pembrolizumab. Case 2. A 60-year-old man with advanced strongly PD-L1-positive lung adenocarcinoma was treated with combined therapy of pembrolizumab and cytotoxic chemotherapy after surgical resection of a brain metastasis. No tumor progression was observed at 41 months after starting antineoplastic therapy. Conclusion. In both cases, the symptoms and quality of life were improved via surgical resection for symptomatic solitary brain metastasis, and a long-term survival was achieved with antineoplastic therapy.

Background. Patients with non-small cell lung cancer on hemodialysis have limited treatment options, and the prognosis is often severe because standard treatment cannot be administered. Case. A 70-year-old man with chronic kidney dysfunction was diagnosed with cT2aN1M0 stage IIB non-small cell lung cancer, and thoracoscopic left upper lobe resection was performed. One year later, recurrence due to liver metastasis was detected and pembrolizumab was administered as first-line therapy because the tumor showed a high PD-L1 expression level. Hemodialysis was introduced during treatment, and pembrolizumab treatment led to a partial response. After 11 courses of pembrolizumab, liver metastasis increased. The patient was subsequently treated with four courses of carboplatin and nab-paclitaxel as second-line therapy, which resulted in a partial response. Although blood transfusion was required for grade 3 anemia, the adverse events were manageable, end the patient was discharged from hospital. The third and fourth courses of treatment were continued as outpatient treatment. Conclusion. Combination chemotherapy with carboplatin and nab-paclitaxel after progression on pembrolizumab may be administered for patients with non-small cell lung cancer who are receiving hemodialysis, as it is efficient and tolerable.